DESCRIPTION (provided by principal investigator): Pelvic Inflammatory Disease (PID) is a common disease among young women that results in serious sequelae including infertility, recurrence, and chronic pelvic pain. Although Neisseria gonorrhoeae and/or Chlamydia trachomatis are recovered from approximately a third to a half of women with PID, in the other women the etiologic agent is often unidentified. Several studies have linked bacterial vaginosis (BV) with PID, but the role of several newly identified BV-associated bacteria, such as Leptotrichia sanguinegens/amnionii, Atopobium vaginae, and Bacterial Vaginosis Associated Bacteria (BVAB) in PID has been little studied. The mycoplasma U. urealyticum has been associated with PID and infertility, although with mixed results. Recently, U. urealyticum has been split into two biovars, U. parvum (biovar 1), which has been found to be nonpathogenic in men in some studies, and U. urealyticum (biovar 2, UU-2), which has been associated with urethritis in men. The role of UU-2 in reproductive disease in women is understudied. The great majority of American women with suspected PID are treated with antibiotic regimens directed toward gonorrheal and chlamydial PID. Mycoplasmas have demonstrated considerable resistance to tetracyclines, and little is known about the treatment of newly identified BV pathogens. We propose that women infected with these bacteria in the upper genital tract who are treated with current PID regimens may experience persistent infection and reproductive morbidity. We propose a polymerase chain reaction (PCR) study of Leptotrichia sanguinegens/amnionii, A. vaginae, BVAB, and UU-2 among 831 women in the ongoing PID Evaluation and Clinical Health Study. Using stored baseline and 30 day cervical and endometrial specimens, we propose to: 1) identify the risk factors for infections of the lower and upper genital tract;2) determine the associations between these pathogens, endometritis, and cervicitis;3) determine the associations between these bacteria and BV;4) assess the treatment response of these infections to cefoxitin and doxycycline;and 5) evaluate the impact of these infections on reproductive morbidity. Exploring the role of novel pathogens in PID is imperative to optimize diagnosis and treatment and to prevent reproductive morbidity among women with nongonococcal/nonchlamydial PID. PUBLIC HEALTH RELEVANCE: The proposed study will be the first to compare infertility, chronic pelvic pain, and recurrent pelvic inflammatory disease (PID) in PID patients treated with currently recommended anti-microbial regimens. Given the scarcity of information regarding the effectiveness of current PID treatment for women with L. sanguinegens/amnionii, A. vaginae, BVAB, UP, and UU-2, the proposed study is imperative in order to optimize treatment for all women with PID and design targeted intervention strategies, whether of chlamydial/gonococcal or anaerobic origin. Knowledge of the risk factors, clinical characteristics, treatment efficacy, and morbidity of L. sanguinegens/amnionii, A. vaginae, BVAB, and UU-2 PID will direct future clinical and public health recommendations.